The relationship between menopausal status and total serum cholesterol was examined cross-sectionally in a population of 40- to 54-year-old black and white women of Evans County, Georgia. The relationship differed in blacks and whites as assessed by a significant interaction term in linear regression. Controlling for age, Quetelet index, and smoking status, white postmenopausal women showed an estimated increase in total serum cholesterol of 25 mg/dl (p less than 0.001) compared with premenopausal whites, whereas black postmenopausal women showed no significant increase in total serum cholesterol compared with premenopausal blacks. The authors were unable to attribute the lack of menopausal effect in blacks to selection or measurement bias, nor did confounding or effect modification by obesity or social status negate their findings. Of six other populations in which menopausal influence on total serum cholesterol has been examined, only Pima Indians failed to show a significant increase.